Tandem fourier transform ion cyclotron resonance mass spectrometer

ABSTRACT

A tandem Fourier transform ion cyclotron resonance mass spectrometer is provided. In the mass spectrometer, the ions selected by a FT-ICR mass analyzer, which can perform an ion selection process and a mass measurement process with a time interval between the processes, are transmitted through an ion guide to a collision cell, which is located a predetermined distance from the FT-ICR mass analyzer, to split into fragment ions. The fragment ions are transmitted to the FT-ICR mass analyzer that measures the mass of the fragment ions. The fragment ions are generated in the collision cell  60  established separately from the FT-ICR mass analyzer  40  according to the mass spectrometer. Accordingly, It can solve various problems (e.g., the radius reduction of cyclotron motion of colliding ions, or the removal of periphery gas after generating the fragment ions) occurred in a tandem mass spectrometer using a conventional tandem-in-time mass analysis method. Also, a high resolution and with sensitivity measurement can be achieved. Moreover, when a reagent gas instead of a collision gas in the collision cell is injected, the gas phase reaction of the selected ions and the reagent gas can be observed, and the mass of the ions generated in the gas phase reaction can be measured.

TECHNICAL FIELD

The present invention relates to a mass spectrometer, and moreparticularly, to a tandem Fourier transform ion cyclotron resonance massspectrometer.

BACKGROUND ART

A mass spectrometer is an apparatus for detecting the molecularstructure of a test sample by selecting molecular ions formed by anionization source and measuring the mass of the fragment ions with amass analyzer, wherein the ionization source ionizes the test sampleusing electrospray ionization (ESI) and matrix assists laser desorptionionization (MALDI) methods, and the mass analyzer includes an ion trapanalyzer, time-of-flight analyzer, quadrupole analyzer and Fouriertransform ion cyclotron resonance (FT-ICR) analyzer.

A tandem mass spectrometer uses a combination of one or more differenttypes of the various mass analyzers, and is classified into a tandemmass spectrometer using a tandem-in-space mass analysis method and atandem mass spectrometer using a tandem-in-time mass analysis method.

The tandem mass spectrometer using the tandem-in-space mass analysismethod generally uses the quadrupole analyzer and the ion trap analyzer.One of two mass analyzers spaced apart from each other selects andseparates ions that will be measured, and then transmits the separatedions to a collision cell having a collision gas. The other of the twoseparate mass analyzers measures the mass of fragment ions transmittedfrom the collision cell, wherein the fragment ions are generated bycolliding the separated ions with the collision gas.

The tandem mass spectrometer using the tandem-in-time mass analysismethod uses a trap type mass analyzer such as a FT-ICR analyzer, andperforms an ion selection process and a mass measurement process with atime interval in the same mass analyzer.

The tandem mass spectrometer using the tandem-in-space mass analysismethod generally has a low resolution in selecting the ions with aspecific mass, thus having a limitation in selecting and separating theions of the specific mass with high resolution. The resolution iscalculated by dividing the width at half height of a peak in a massspectrum by the value of m/z (mass-to-charge ratio) at the peak.

The tandem mass spectrometer using the tandem-in-time mass analysismethod can select the ions with a specific mass at high resolution in aFT-ICR trap using a FT-ICR analyzer. In this case, an inert collisiongas is injected into the FT-ICR trap for generating fragment ions, thefragment ions are generated by colliding the inert collision gas withthe ions selected by the FT-ICR mass analyzer, and the masses of thegenerated fragment ions are measured in the FT-ICR trap.

However, in the tandem mass spectrometer using the tandem-in-time massanalysis method, the radius of ion cyclotron motion is reduced becausethe peripheral pressure in the FT-ICR trap is increased by injecting theinert collision gas. Accordingly, the magnitude of ion detection signalis gradually decreased and the resolution and the magnitude of a massspectrum are reduced.

Also, the peripheral gas in the FT-ICR trap must be removed aftergenerating the fragment ions and thus the mass of the fragment ionscannot be measured quickly.

DISCLOSURE OF INVENTION Technical Problem

Accordingly, the present invention is directed to a tandem Fouriertransform ion cyclotron resonance mass spectrometer that substantiallyobviates one or more of the problems due to limitations anddisadvantages of the related art.

An object of the present invention is to provide a tandem Fouriertransform ion cyclotron resonance mass spectrometer transmitting theions selected by a FT-ICR mass analyzer, which can perform an ionselection process and a mass measurement process with a time intervalbetween the processes, through an ion guide to a collision cell, whichis located at a predetermined distance from the FT-ICR mass analyzer, tosplit into fragment ions. The fragment ions are transmitted to theFT-ICR mass analyzer that measures the mass of the fragment ions.

Technical Solution

To achieve these and other advantages and in accordance with the purposeof the present invention, as embodied and broadly described, there isprovided a tandem Fourier transform ion cyclotron resonance massspectrometer including: an ionization source for ionizing a sampleinjected in a gaseous state or the like and ejecting ions, a skimmer formaintaining a vacuum state for the ions ejected from the ionizationsource, a first ion guide for transmitting the ions inflowed through theskimmer, a FT-ICR mass analyzer for selecting the ions with a specificmass among the ions inflowed through the first ion guide, and measuringthe mass of fragment ions of the selected ions, a second ion guide fortransmitting the ions selected by the FT-ICR mass analyzer, a collisioncell for colliding the selected ions inflowed through the second ionguide with a collision gas injected through a collision gas injectionport to generate fragment ions and transmitting the fragment ions to theFT-ICR mass analyzer through the second ion guide, and a vacuum pump formaintaining a vacuum state in the interior of the ionization source, theskimmer, the first ion guide, the FT-ICR mass analyzer, the second ionguide, the collision gas injection port and the collision cell.

Advantageous Effects

As described above, a tandem Fourier transform ion cyclotron resonancemass spectrometer according to the present invention can select ions athigh resolution by performing an ion selection process in a FT-ICR massanalyzer. Also, the fragment ions are generated in the collision cellestablished separately from the FT-ICR mass analyzer. This can solvevarious problems (e.g., the radius reduction of cyclotron motion ofcolliding ions, or the removal of periphery gas after generating thefragment ions) occurred in a tandem mass spectrometer using aconventional tandem-in-time mass analysis method, thereby achieving thehigh resolution and high-sensitivity measurement.

Moreover, when a reagent gas instead of a collision gas in the collisioncell is injected, the gas phase reaction of the selected ions and thereagent gas can be observed, and the mass of the ions generated in thegas phase reaction can be measured.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a block diagram of a tandem Fourier transform ion cyclotronresonance mass spectrometer; and

FIG. 2 is a schematic sectional view of a tandem Fourier transform ioncyclotron resonance mass spectrometer.

DESCRIPTION OF SYMBOLS IN MAIN PARTS OF THE DRAWINGS

-   -   10: ionization source    -   20: skimmer    -   30: first ion guide    -   40: FT-ICR mass analyzer    -   41: cylindrical superconducting magnet    -   42: FT-ICR trap    -   50: collision gas injection port    -   60: collision cell    -   70: vacuum pump

BEST MODE FOR CARRYING OUT THE INVENTION

Hereinafter, preferred embodiments of the present invention will bedescribed in detail with reference to accompanying drawings.

Referring to FIGS. 1 and 2, an ionization source 10 ionizes a sampleinjected in a gaseous state or the like into molecular ions, and ejectsthe molecular ions.

A skimmer 20 allows the ions ejected from the ionization source 10 to betransmitted to a first ion guide 30 in a vacuum state.

The first ion guide 30 transmits to a FT-ICR mass analyzer 40 the ionsthat are ejected from the ionization source 10 and inflowed into thefirst ion guide 30 through the skimmer 20.

The FT-ICR mass analyzer 40 selects the ions with a specific mass amongthe ions inflowed through the first ion guide 30, and measures the massof fragment ions that are generated in a collision cell 60 and inflowedthrough a second ion guide 30′.

The FT-ICR mass analyzer 40 includes a cylindrical superconductingmagnet 41, and an ion selection and mass measurement FT-ICR trap 42located inside the magnet 41.

The FT-ICR mass analyzer 40 may include the cylindrical superconductingmagnet 41, an ion selection FT-ICR trap (not shown), and a massmeasurement FT-ICR trap (not shown).

When an ion selection FT-ICR trap and a mass measurement FT-ICR trap areseparated in the FT-ICR trap, the mass measurement FT-ICR trap may belager in volume than the ion selection FT-ICR trap to improve themeasurement sensitivity of an ion.

Using an arbitrary waveform generator (AWG), the FT-ICR mass analyzer 40selects the ions with a specific mass at a high resolution of5000˜100000 by ejecting the ions in a predetermined mass range.

Using a stored waveform inverse Fourier transform (SWIFT) technique, theFT-ICR mass analyzer 40 selects the ions with a specific mass at aresolution of 5000˜100000 by increasing the radius of ion cyclotronmotion and ejecting undesired ions. The SWIFT technique is summarized asfollows: a waveform of frequencies reactive to a desired ion mass rangeis selected, and a waveform function in time domain is generated usinginverse Fourier transform.

The second ion guide 30′ transmits the ions selected by the FT-ICR massanalyzer 40 to the collision cell 60.

The collision cell 60 allows the selected ions inflowed through thesecond guide 30′ to collide with a collision gas injected through acollision gas injection port 50. Then, fragment ions are generated. Thegenerated fragment ions are transmitted to the FT-ICR mass analyzer 40through the second ion guide 30′.

After ions selected by the FT-ICR mass analyzer 40 are inflowed into thecollision cell 60 through the second ion guide 30′, a specific reagentgas reactive to the selected ions may be injected through the collisiongas injection port 50. Then, a gas phase reaction of the selected ionsand the reagent gas is carried out. Ions generated in the gas phasereaction may be transmitted to the FT-ICR mass analyzer 40, and theFT-ICR mass analyzer 40 can measure the mass of the ions generated inthe gas phase reaction.

A vacuum pump 70 maintains a vacuum state in the interior of theionization source 10, the skimmer 20, the first ion guide 30, the FT-ICRmass analyzer 40, the second ion guide 30′, the collision gas injectionport 50 and the collision cell 60.

A description will be given of the operation of the tandem Fouriertransform ion cyclotron resonance mass spectrometer including the abovecomponents according to the present invention.

A sample is injected into the ionization source 10 in a gaseous state orthe like, and then the ionization source 10 ionizes a sample and ejectsions generated by the ionization source 10.

The skimmer 20 allows the ions ejected from the ionization source 10 tobe transmitted to the first ion guide 30 in a vacuum state. The ions aretransmitted to the FT-ICR trap 42 located inside the cylindricalsuperconducting magnet 41 of the FT-ICR mass analyzer 40 through thefirst ion guide 30.

The FT-ICR mass analyzer 40 selects the ions with a specific mass formeasurement among the ions inflowed through the first ion guide 30.

Using an AWG, the FT-ICR mass analyzer 40 selects the ions with aspecific mass at a high resolution of 5000˜100000 by ejecting the ionsin a predetermined mass range.

Using a SWIFT technique, the FT-ICR mass analyzer 40 selects the ionswith a specific mass at a resolution of 5000˜100000 by increasing theradius of ion cyclotron motion and ejecting undesired ions. The SWIFTtechnique is summarized as follows: a waveform of frequencies reactiveto a desired ion mass range is selected, and a waveform function in timedomain is generated using inverse Fourier transform.

As described above, when the ions with a specific mass for measurementare selected, the FT-ICR mass analyzer 40 transmits the selected ions tothe collision cell 60 via the second ion guide 30′.

The collision cell 60 collides the selected ions inflowed through thesecond ion guide 30′ with a collision gas (e.g., neutral gas such asnitrogen and argon) injected through a collision gas injection port 50to generate fragment ions. The collision cell 60 transmits the fragmentions to the FT-ICR mass analyzer 40 through the second ion guide 30′.

As described above, fragment ions are generated in the collision cell 60established separately from the FT-ICR mass analyzer 40 by colliding theions selected by the FT-ICR mass analyzer 40 with a collision gas. Itcan solve various problems (e.g., the radius reduction of cyclotronmotion of colliding ions, or the removal of periphery gas aftergenerating fragment ions) occurred in a tandem mass spectrometer using aconventional tandem-in-time mass analysis method. Accordingly, highresolution and high sensitivity measurement can be achieved.

When fragment ions generated in the collision cell 60 are inflowed intothe FT-ICR mass analyzer 40 through the second ion guide 30′, the FT-ICRmass analyzer 40 allows a magnetic field reactive to a resonancefrequency to be produced in the FT-ICR trap 42. The fragmented ions havea cyclotron motions in the direction perpendicular to the magneticfield. The masses of various ions can be measured simultaneously andprecisely by measuring an image current induced by the fragment ions atelectrodes of the FT-ICR trap 42.

In operation of a tandem Fourier transform ion cyclotron resonance massspectrometer according to the present invention, when the FT-ICR massanalyzer 40 selects the ions with a specific mass for measurement, andtransmits the selected ions to the collision cell 60 through the secondion guide 30′, a specific reagent gas reactive to the selected ionsinstead of a collision gas is injected to the collision cell 60, andthen a gas phase reaction of the selected ions and the reagent gas(e.g., the interchange reaction of hydrogen with deuterium) can beobserved in the interior of the collision cell 60.

Also, the ions generated in the gas phase reaction are transmitted tothe FT-ICR mass analyzer 40, and the mass of the generated ions can bemeasured.

For example, protein ions generated by the interchange reaction of ahydrogen with a deuterium may be transmitted to the FT-ICR mass analyzer40 to measure the mass of the protein ions. Accordingly, the structuralinformation of a proteins and a protein complex can be obtained.

It will be apparent to those skilled in the art that variousmodifications and variations can be made in the present invention. Thus,it is intended that the present invention covers the modifications andvariations of this invention provided they come within the scope of theappended claims and their equivalents.

1. A tandem Fourier transform ion cyclotron resonance mass spectrometercomprising: an ionization source for ionizing a sample and ejectingions; a skimmer for maintaining a vacuum state for the ions ejected fromthe ionization source; a first ion guide for transmitting the ionsinflowed through the skimmer; a FT-ICR mass analyzer for selecting theions with a specific mass among the ions inflowed through the first ionguide, and measuring the mass of fragment ions of the selected ions; asecond ion guide for transmitting the ions selected by the FT-ICR massanalyzer; a collision cell for colliding the selected ions inflowedthrough the second ion guide with a collision gas injected through acollision gas injection port to generate the fragment ions andtransmitting the fragment ions to the FT-ICR mass analyzer through thesecond ion guide; and a vacuum pump for maintaining a vacuum state inthe interior of the ionization source, the skimmer, the first ion guide,the FT-ICR mass analyzer, the second ion guide, the collision gasinjection port and the collision cell.
 2. The apparatus of claim 1,wherein the FT-ICR mass analyzer comprises a cylindrical superconductingmagnet and an ion selection and mass measurement FT-ICR trap locatedinside the cylindrical superconducting magnet.
 3. The apparatus of claim1, wherein the FT-ICR mass analyzer comprises a cylindricalsuperconducting magnet, an ion selection FT-ICR trap and a massmeasurement FT-ICR trap located inside the cylindrical superconductingmagnet.
 4. The apparatus of claim 3, wherein the FT-ICR mass analyzeruses an AWG (arbitrary waveform generator) to select the ions with aspecific mass at a high resolution of 5000˜100000 by ejecting the ionsin a predetermined mass range.
 5. The apparatus of claim 3, wherein theFT-ICR mass analyzer uses a SWIFT (stored waveform inverse Fouriertransform) technique to select the ions with a specific mass at aresolution of 5000˜100000 by increasing the radius of ion cyclotronmotion and ejecting undesired ions, the SWIFT technique being summarizedas follows: a waveform of frequencies reactive to a desired ion massrange is selected, and a waveform function in time domain is generatedusing inverse Fourier transform.
 6. The apparatus of claim 1, whereinthe collision cell injects a specific reagent gas reactive to the ionsselected by the FT-ICR mass analyzer through the collision gas injectionport after the selected ions are inflowed into the collision cellthrough the second ion guide induces the gas phase reaction of theselected ions and the reagent gas, and transmits the ions generated inthe gas phase reaction to the FT-ICR mass analyzer to allow the FT-ICRmass analyzer to measure the mass of the ions generated in the gas phasereaction.
 7. The apparatus of claim 2, wherein the FT-ICR mass analyzeruses an AWG (arbitrary waveform generator) to select the ions with aspecific mass at a high resolution of 5000˜100000 by ejecting the ionsin a predetermined mass range.
 8. The apparatus of claim 1, wherein theFT-ICR mass analyzer uses an AWG (arbitrary waveform generator) toselect the ions with a specific mass at a high resolution of 5000˜100000by ejecting the ions in a predetermined mass range.
 9. The apparatus ofclaim 2, wherein the FT-ICR mass analyzer uses a SWIFT (stored waveforminverse Fourier transform) technique to select the ions with a specificmass at a resolution of 5000˜100000 by increasing the radius of ioncyclotron motion and ejecting undesired ions, the SWIFT technique beingsummarized as follows: a waveform of frequencies reactive to a desiredion mass range is selected, and a waveform function in time domain isgenerated using inverse Fourier transform.
 10. The apparatus of claim 1,wherein the FT-ICR mass analyzer uses a SWIFT (stored waveform inverseFourier transform) technique to select the ions with a specific mass ata resolution of 5000˜100000 by increasing the radius of ion cyclotronmotion and ejecting undesired ions, the SWIFT technique being summarizedas follows: a waveform of frequencies reactive to a desired ion massrange is selected, and a waveform function in time domain is generatedusing inverse Fourier transform.